Between 1973 and 1995 the incidence of rectal cancer decreased 2.0 percent in blacks compared to 20.2 percent in whites. From 1989-94, the five-year relative survival was 52.5 percentin blacks and 63.0 percent in whites. These differences have not been explained. In fact, black-white differences in rectal cancer incidence and mortality have not been adequately studied. This competing renewal application seeks funds to conduct a population-based study of rectal cancer in blacks and whites in a 33-county area of North Carolina, building on the infrastructure developed in an ongoing and successful study of colon cancer. The primary goal of the proposed research is to examine possible exposure, susceptibility, and health care factors that might explain diverging incidence and mortality trends in blacks and whites. The specific aims of this research are: (1) To identify environmental and lifestyle risk factors for rectal cancer in blacks and whites. The proposed study will explore a range of exposures that may be related to rectal cancer. (2) To assess the prevalence and etiologic importance of specific inherited susceptibility characteristics in a large mixed-race population. The study will focus on the known alleles of the N-acetyltransferase genes (NAT1 and NAT2) and manganese superoxide dismutase (MnSOD) genes using DNA obtained from blood samples. The study will investigate interactions between these genes and environmental exposures. (3) To evaluate factors that might account for the higher mortality among blacks including poverty, insurance, access to care, delay in the medical system, and transportation. A secondary aim is to collect biological specimens for subsequent analyses such as the role of other inherited genetic characteristics and the presence or absence of specific somatic genetic alterations. The study will recruit 1000 cases of rectal cancer age 40-80 and 1000 population-based controls. Cancer cases (250 blacks and 750 whites) will be identified using the rapid ascertainment system of the North Carolina Central Cancer Registry. Controls (250 blacks and 750 whites) will be selected using Division of Motor Vehicle Registry data for those under age 65 and HCFA files for those age 65 and over. Dietary, lifestyle and environmental exposure information will be obtained for cases and controls by personal, in-home interviews. The interview instrument includes comprehensive questions concerning diet and the use of dietary supplements, and seeks information about medications, education, physical activity, poverty, health care access and utilization. DNA extracted from peripheral blood lymphocytes will be used to determine NAT and MnSOD genotypes.